RRC ID 44277
著者 Obara G, Toyohira Y, Inagaki H, Takahashi K, Horishita T, Kawasaki T, Ueno S, Tsutsui M, Sata T, Yanagihara N.
タイトル Pentazocine inhibits norepinephrine transporter function by reducing its surface expression in bovine adrenal medullary cells.
ジャーナル J Pharmacol Sci
Abstract (±)-Pentazocine (PTZ), a non-narcotic analgesic, is used for the clinical management of moderate to severe pain. To study the effect of PTZ on the descending noradrenergic inhibitory system, in the present study we examined the effect of [(3)H]norepinephrine (NE) uptake by cultured bovine adrenal medullary cells and human neuroblastoma SK-N-SH cells. (-)-PTZ and (+)-PTZ inhibited [(3)H]NE uptake by adrenal medullary cells in a concentration-dependent (3-100 μM) manner. Eadie-Hofstee analysis of [(3)H]NE uptake showed that both PTZs caused a significant decrease in the V(max) with little change in the apparent K(m), suggesting non-competitive inhibition. Nor-Binaltorphimine and BD-1047, κ-opioid and σ-receptor antagonists, respectively, did not affect the inhibition of [(3)H]NE uptake induced by (-)-PTZ and (+)-PTZ, respectively. PTZs suppressed specific [(3)H]nisoxetine binding to intact SK-N-SH cells, but not directly to the plasma membranes isolated from the bovine adrenal medulla. Scatchard analysis of [(3)H]nisoxetine binding to SK-N-SH cells revealed that PTZs reduced the B(max) without changing the apparent K(d). Western blot analysis showed a decrease in biotinylated cell-surface NE transporter (NET) expression after the treatment with (-)-PTZ. These findings suggest that PTZ inhibits the NET function by reducing the amount of NET in the cell surface membranes through an opioid and σ-receptor-independent pathway.
巻・号 121(2)
ページ 138-47
公開日 2013-1-1
DOI 10.1254/jphs.12164fp
PII DN/JST.JSTAGE/jphs/12164FP
PMID 23370666
MeSH Adrenal Medulla / diagnostic imaging Adrenal Medulla / drug effects Adrenal Medulla / metabolism Analgesics, Opioid / pharmacology* Animals Cattle Cell Line Cell Membrane / diagnostic imaging Cell Membrane / drug effects Cell Membrane / metabolism Cells, Cultured Ethylenediamines / pharmacology Fluoxetine / analogs & derivatives Fluoxetine / pharmacology Gene Expression / drug effects Humans Naltrexone / analogs & derivatives Naltrexone / pharmacology Narcotic Antagonists / pharmacology* Norepinephrine / metabolism Norepinephrine Plasma Membrane Transport Proteins / antagonists & inhibitors* Norepinephrine Plasma Membrane Transport Proteins / metabolism* Pentazocine / pharmacology* Radionuclide Imaging
IF 2.835
引用数 6
WOS 分野 PHARMACOLOGY & PHARMACY
リソース情報
ヒト・動物細胞 COS-7(RCB0539) SK-N-SH(RCB0426)